Neuroprotective effect of α-mangostin in MPTP-induced parkinson's disease in mice: oxidative stress parameters

Neurodegeneration is the progressive damage of nerve cell. Parkinson's disease (PD) is one of neurodegenerative disease due to the loss of dopaminergic neuron in the substantia nigra portion of pars compacta. PD symptoms can be induced into mice by l-methyl-4-phenyl-l, 2, 3, 6-tetrahydropyridine (MPTP), a neurotoxin by converting to l-ethyl-4-phenylpyridinium (MPP+) and enter the dopaminergic neuron. Then, it will inhibit the mitochondrial electron transport chain and deplete the ATP production which leads to cell death. α-Mangostin is a xanthone derivative isolated from natural sources that has a neuroprotective effect against neurodegenerative disease such as PD, found in the pericarp of mangosteen (Mangostana garcinia Linn) fruit. α-Mangostin can scavenge the reactive oxygen species (ROS) and prevent lipid peroxidation. Hence, the study was carried out to determine whether α-Mangostin can inhibit the oxidative stress in MPTP-induced PD in mice. Animals were divided into 6 groups (n=7). MPTP (10 mg/kg, i.p.) was administered four times (day 1, day 3, day 5 and day 7) throughout the study. α-Mangostin (3 and 6 mg/kg, p.o.), standard drug (Sinemet, p.o.) and L-NAME (5 mg/kg, i.p.) were given for another 7 days (day 8 - day 15). Then, mice were sacrificed and brain was removed out and homogenized for measurement of lipid peroxidation, levels of superoxide dismutase (SOD), reduced glutathione (GSH) and nitric oxide (NO). The results showed that α-mangostin (3 & 6 mg/kg) was able to inhibit lipid peroxidation, increase GSH and SOD levels which contributed to the protective effect against the oxidative stress induced by MPTP. The antioxidant effects may be due to the presence of the hydroxyl groups of the compound. In conclusion, n-mangostin has neuroprotective effect against neurodegeneration in PD by inhibiting oxidative stress through antioxidant mechanism.